- Case report
- Open access
- Published:
First case report of acute cholangitis secondary to Cronobacter sakazakii
BMC Infectious Diseases volume 21, Article number: 493 (2021)
Abstract
Introduction
Cronobacter sakazakii is an opportunistic Gram-negative, rod-shaped bacterium which may be a causative agent of meningitis in premature infants and enterocolitis and bacteremia in neonates and adults. While there have been multiple cases of C. sakazakii infections, there have been no acute cholangitis cases reported in humans.
Case presentation
An 81-year-old male with a past medical history of basal cell carcinoma, alcoholic liver cirrhosis, transjugular intrahepatic portosystemic shunt procedure, complicated by staphylococcus bacteremia, pituitary tumor, glaucoma, and hypothyroidism presented to the emergency room with the complaint of diffuse and generalized 10/10 abdominal pain of 1 day’s duration. There was a concern for pancreatitis, acute cholangitis, and possible cholecystitis, and the patient underwent a percutaneous cholecystostomy tube placement. Blood cultures from admission and biliary fluid cultures both grew C. sakazakii. The patient was treated with a carbapenem and clinically improved.
Conclusions
The case study described a patient with multiple medical comorbidities that presented with C. sakazakii bacteremia and cholangitis. While this bacterium has been implicated in other infections, we believe this is the first time the bacteria is being documented to have caused acute cholangitis.
Background
C. sakazakii is responsible for life-threatening infections, including meningitis and brain abscesses with potentially permanent neurological sequelae for the neonatal population. The CC4 variant of Cronobacter has been associated with necrotizing enterocolitis as well. Urinary tract infections, septicemia, and lung and wound infections are reported in adults, particularly in those with underlying immunocompromising comorbidities. We present the first case of acute cholangitis in an elderly male where C. sakazakii was reported on the PCR assay of cultures from blood and biliary fluid. This is the first case of C. sakazakii in the medical literature where it caused cholangitis in an adult patient to the best of our knowledge. The patient responded well to therapy with a carbapenem. Infection with C. sakazakii should be considered in cholangitis in the elderly population with comorbidities not responsive to cephalosporins.
Case presentation
An 81-year-old male came to E.R. with the complaint of abdominal pain of 1 day’s duration. His past medical records were significant for basal cell carcinoma, alcoholic liver cirrhosis with a history of an intrahepatic portosystemic shunt procedure, complicated by staphylococcus bacteremia, pituitary tumor, glaucoma, and hypothyroidism. The abdominal pain had been constant, non-radiating, diffuse, burning in nature, 10/10 in intensity, and associated with chills. He denied any associated fevers, cough, nausea, vomiting, diarrhea, chest pain, headaches, shortness of breath, recent travels, or sick contacts.
On physical examination, his temperature was 98 °F, pulse 104 bpm, blood pressure 133/74 mmHg, respiratory rate 18 beats per minute, O2 saturation 99%. An abdominal exam revealed an obese body habitus, distention, and periumbilical tenderness with a negative Murphy’s sign.
Initial blood work showed normal leukocyte count white blood cells (WBC) 4.5 K/uL, Creatinine 1.2 mg/dL, elevated aspartate aminotransferase (A.S.T.) 62 U/L, elevated Lipase 451 u/L, elevated Lactate 8.8 mmol/L, and normal serum levels of alanine aminotransferase (A.L.T.) 28 U/L, Alkaline Phosphatase 99 U/L, and total serum bilirubin 1.1 mg/dL. The sonogram and C.T. scan of the abdomen revealed perihepatic ascites, nodular liver contour, cholelithiasis, and gallbladder sludge with mild gallbladder wall thickening up to 4 mm without any radiographic evidence of acute cholecystitis (Figs. 1 and 2).
The patient was not a surgical candidate due to his advanced age and multiple comorbidities, and a CT-guided percutaneous cholecystotomy was performed for drainage of biliary fluid by Interventional Radiology. The biliary fluid was sent for culture, and cefepime and metronidazole were started empirically.
On the second day of hospitalization, the periumbilical pain improved, but right upper quadrant tenderness increased, and Murphy’s sign was elicited. The patient concurrently developed fever, leukocytosis (16.5 k/uL) with predominant neutrophilia (81%), and worsening acute kidney injury. Blood specimens drawn on admission were positive for gram-negative rods, which speciated to C. sakazakii on PCR studies. The PCR assay was performed using BioFire FilmArray.
Body fluid samples underwent protein extraction, priming, and drying before matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry was applied to the resultant intact cells and extracts from cells. Identification targets other than C. sakazakii were Enterococcus including vancomycin-resistant Enterococcus, L. monocytogenes, coagulase-negative Staphylococcus, S. aureus, S. agalactiae (Group B), S. pneumoniae, S. pyogenes (Group A), A. baumannii, E. cloacae, E. coli, K. oxytoca, K. pneumoniae, Proteus sp., S. marcescens, H. influenzae, N. meningitidis, P. aeruginosa, C. albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis and the K. pneumoniae carbapenemase (KPC) resistant gene. Microflex L.T. and MADLI Biotyper by Bruker Daltonics, Germany was employed in our institutional laboratory for mass spectrometry measurements and microorganism identification. The same organism was found in the biliary drain culture, confirming acute cholangitis due to C. sakazakii complicated by bacteremia. Susceptibilities of C. sakazakii were obtained against 17 antibiotics (Figs. 3 and 4).
Antibiotic coverage was consequently expanded to IV meropenem. His clinical picture and blood work improved exponentially with a downtrend of leukocytes, lactate, lipase, bilirubin, and liver enzymes (Table 1). He was discharged home on hospital day seven on oral ciprofloxacin and metronidazole for 10 days and was reported doing well on telephonic follow-up. The patient was later seen in outpatient clinics (Surgery and Infectious diseases) 2 weeks later. He was asymptomatic without any residual disease, and the biliary drain was removed successfully. The patient underwent an elective cholecystectomy a few weeks later with no complications.
Discussion and conclusions
C. sakazakii, previously called Enterobacter sakazakii, has been notorious since the 1980s for its fatal complications, including meningitis, hydrocephalus, and brain abscess in the neonatal population [1, 2]. C. sakazakii infections, including urinary tract infections, bacteremia, osteomyelitis, splenic abscess, and wound infections, have been reported in the adult population, particularly in those with immunocompromising conditions [3,4,5,6,7]. A clinical study on stroke patients associated it with aspiration pneumonia as higher oral C. sakazakii inoculums were reported in patient cohorts [8].
C. sakazakii has been reported in the human gastrointestinal tract, domestic and nosocomial settings, laboratory samples, and food items [9,10,11,12,13]. Bacterial contamination of infant formula milk was thought accountable for outbreaks in the neonatal population [14,15,16,17,18,19]. Studies have been done and are in the process of establishing the true etiology and source of C. sakazakii, which previously had been a diagnostic challenge leading to lesser reporting [20].
The case presented is the first case of cholangitis secondary to C. sakazakii in humans. There was no radiographic evidence of cholecystitis. The source of this Gram-negative rod invasion could be from the patient’s gastrointestinal flora. Basal cell carcinoma, liver cirrhosis, advanced age, and being on long-term steroid maintenance therapy could have contributed to immunosuppression and exponential growth of the opportunistic pathogen in the colon. Studies have reported C. sakazakii in pig gallbladder, hinting towards the gallbladder being a potential site of colonization and the risk of contracting C. sakazakii from consuming pork meat [21]. We could not rule out a dietary source in this patient. Sample contamination or infection with opportunistic gastrointestinal pathogens including Klebsiella, Acinetobacter, and E. coli were ruled out as C. sakazakii with similar antibiotic sensitivity was found on PCR studies for both blood biliary fluid. Besides, there was a dramatic response to optimum antibiotic treatment.
Carbapenems have been particularly efficient as C. sakazakii is resistant to ampicillin and the majority of cephalosporins [22]. Resistance to ampicillin was reported on antibiotic susceptibility testing for this organism as well. Ceftazidime, cephalothin, and cefotaxime were not added to the antibiotic sensitivity panel, which is a shortcoming in this case. The case raises the fact that C. sakazakii is a potential causative organism for gallbladder infections, particularly in elderly populations with underlying comorbidities. In conclusion, this case is significant in its clinical manifestation, causative pathogen, infection site, and treatment.
Availability of data and materials
The datasets used and/or analyzed during the current case reports are available from the corresponding author on reasonable request.
Abbreviations
- E.R.:
-
Emergency room
- MALDI-TOF MS:
-
Matrix-assisted laser desorption ionization-time of flight mass spectrometry
References
Chaves CEV, Brandão MLL, Lacerda MLGG, Rocha CABC, Leone de Oliveira SMV, Parpinelli TC, et al. Fatal cronobacter sakazakii sequence type 494 meningitis in a newborn, Brazil. Emerg Infect Dis. 2018;24(10):1948–50. https://doi.org/10.3201/eid2410.180373.
Burdette JH, Santos C. Enterobacter sakazakii brain abscess in the neonate: the importance of neuroradiologic imaging. Pediatr Radiol. 2000;30(1):33–4. https://doi.org/10.1007/s002470050009.
Alsonosi A, Hariri S, Kajsík M, Oriešková M, Hanulík V, Röderová M, et al. The speciation and genotyping of Cronobacter isolates from hospitalised patients. Eur J Clin Microbiol Infect Dis. 2015;34(10):1979–88. https://doi.org/10.1007/s10096-015-2440-8.
Lai KK. Enterobacter sakazakii infections among neonates, infants, children, and adults. Case reports and a review of the literature. Medicine (Baltimore). 2001;80(2):113–22. https://doi.org/10.1097/00005792-200103000-00004.
Healy B, Cooney S, O'Brien S, Iversen C, Whyte P, Nally J, et al. Cronobacter (Enterobacter sakazakii): an opportunistic foodborne pathogen. Foodborne Pathog Dis. 2010;7(4):339–50. https://doi.org/10.1089/fpd.2009.0379.
Hawkins RE, Lissner CR, Sanford JP. Enterobacter sakazakii bacteremia in an adult. South Med J. 1991;84(6):793–5. https://doi.org/10.1097/00007611-199106000-00033.
Dennison SK, Morris J. Multiresistant Enterobacter sakazakii wound infection in an adult. Infect Med. 2002;19:533–5.
Gosney MA, Martin MV, Wright AE, Gallagher M. Enterobacter sakazakii in the mouths of stroke patients and its association with aspiration pneumonia. Eur J Intern Med. 2006;17(3):185–8. https://doi.org/10.1016/j.ejim.2005.11.010.
Kandhai MC, Reij MW, Gorris LGM, Guillaume-Gentil O, van Schothorst M. Occurrence of Enterobacter sakazakii in food production environments and households. Lancet. 2004;363(9402):39–40. https://doi.org/10.1016/S0140-6736(03)15169-0.
Kandhai MC, et al. A new protocol for the detection of Enterobacter sakazakii applied to environmental samples. J Food Prot. 2004;67(6):1267–70. https://doi.org/10.4315/0362-028X-67.6.1267.
Lehner A, Stephan R. Microbiological, epidemiological, and food safety aspects of Enterobacter sakazakii. J Food Prot. 2004;67(12):2850–7. https://doi.org/10.4315/0362-028X-67.12.2850.
Beuchat LR, Kim H, Gurtler JB, Lin LC, Ryu JH, Richards GM. Cronobacter sakazakii in foods and factors affecting its survival, growth, and inactivation. Int J Food Microbiol. 2009;136(2):204–13. https://doi.org/10.1016/j.ijfoodmicro.2009.02.029.
Friedemann M. Enterobacter sakazakii in food and beverages (other than infant formula and milk powder). Int J Food Microbiol. 2007;116(1):1–10. https://doi.org/10.1016/j.ijfoodmicro.2006.12.018.
van Acker J, de Smet F, Muyldermans G, Bougatef A, Naessens A, Lauwers S. Outbreak of necrotizing enterocolitis associated with Enterobacter sakazakii in powdered milk formula. J Clin Microbiol. 2001;39(1):293–7. https://doi.org/10.1128/JCM.39.1.293-297.2001.
From the Centers for Disease Control and Prevention. Enterobacter sakazakii infections associated with the use of powdered infant formula--Tennessee, 2001. Jama. 2002;287(17):2204–5.
Iversen C, Forsythe S. Risk profile of Enterobacter sakazakii, an emergent pathogen associated with infant milk formula. Trends Food Sci Technol. 2003;14(11):443–54. https://doi.org/10.1016/S0924-2244(03)00155-9.
Forsythe SJ. Updates on the Cronobacter genus. Annu Rev Food Sci Technol. 2018;9(1):23–44. https://doi.org/10.1146/annurev-food-030117-012246.
Chenu JW, Cox JM. Cronobacter (‘Enterobacter sakazakii’): current status and future prospects. Lett Appl Microbiol. 2009;49(2):153–9. https://doi.org/10.1111/j.1472-765X.2009.02651.x.
Drudy D, Mullane NR, Quinn T, Wall PG, Fanning S. Enterobacter sakazakii: an emerging pathogen in powdered infant formula. Clin Infect Dis. 2006;42(7):996–1002. https://doi.org/10.1086/501019.
Lepuschitz S, Ruppitsch W, Pekard-Amenitsch S, Forsythe SJ, Cormican M, Mach RL, et al. Multicenter study of cronobacter sakazakii infections in humans, Europe, 2017. Emerg Infect Dis. 2019;25(3):515–22. https://doi.org/10.3201/eid2503.181652.
Evangelopoulou G, et al. Isolation and antimicrobial testing of aeromonas spp., citrobacter spp., cronobacter spp., enterobacter spp., escherichia spp., klebsiella spp., and trabulsiella spp. from the gallbladder of pigs. Pol J Microbiol. 2015;64(2):185–8. https://doi.org/10.33073/pjm-2015-028.
Holý O, et al. Molecular characterization of cronobacter sakazakii strains isolated from powdered milk. Foods. 2020;10(1):20.
Acknowledgments
Clinical Research Programs SIUH is acknowledged for ethical review for the use of patient data.
Funding
No funding was obtained from any organization or personnel during any stage of manuscript writing or submission.
Author information
Authors and Affiliations
Contributions
Manuscript was written and literature review was obtained by S.S. and A.J. (1). A.G. and N.M. took care of the patient and contributed to the manuscript writing and editing. M.A.S. and A.J. (2) contributing to manuscript writing and revisions. All authors have read and approved the final manuscript.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
The case report and manuscript were reviewed with Research Department and Ethics Committee. No experimental intervention was performed, and any specification of guidelines, legislations, or permissions were not required.
Consent for publication
The patient and family were contacted during the hospital stay and after discharge. Written consent was obtained to use patient data, images, and blood work to publish the case for purely educational and research purposes, to which the patient and family agreed. Non identifying information usage was explained. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Competing interests
No competing financial or personal interests are involved for all the authors.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
Sahra, S., Jahangir, A., Mobarakai, N. et al. First case report of acute cholangitis secondary to Cronobacter sakazakii. BMC Infect Dis 21, 493 (2021). https://doi.org/10.1186/s12879-021-06195-4
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s12879-021-06195-4